Santagati Fabio, Abe Kuniya, Schmidt Volker, Schmitt-John Thomas, Suzuki Misao, Yamamura Ken-Ichi, Imai Kenji
GSF-National Research Center for Environment and Health, Institute of Developmental Genetics, D-85764 Neuherberg, Germany.
Genetics. 2003 Sep;165(1):235-42. doi: 10.1093/genetics/165.1.235.
We previously reported close physical linkage between Pax9 and Nkx2-9 in the human, mouse, and pufferfish (Fugu rubripes) genomes. In this study, we analyzed cis-regulatory elements of the two genes by comparative sequencing in the three species and by transgenesis in the mouse. We identified two regions including conserved noncoding sequences that possessed specific enhancer activities for expression of Pax9 in the medial nasal process and of Nkx2-9 in the ventral neural tube. Remarkably, the latter contained the consensus Gli-binding motif. Interestingly, the identified Pax9 cis-regulatory sequences were located in an intron of the neighboring gene Slc25a21. Close examination of an extended genomic interval around Pax9 revealed the presence of strong synteny conservation in the human, mouse, and Fugu genomes. We propose such an intersecting organization of cis-regulatory sequences in multigenic regions as a possible mechanism that maintains evolutionary conserved synteny.
我们之前报道过，在人类、小鼠和河豚（红鳍东方鲀）基因组中，Pax9与Nkx2-9在物理上紧密连锁。在本研究中，我们通过对这三个物种进行比较测序以及在小鼠中进行转基因操作，分析了这两个基因的顺式调控元件。我们鉴定出两个包含保守非编码序列的区域，它们分别对鼻内侧突中Pax9的表达以及腹侧神经管中Nkx2-9的表达具有特定的增强子活性。值得注意的是，后者包含共有Gli结合基序。有趣的是，所鉴定出的Pax9顺式调控序列位于相邻基因Slc25a21的一个内含子中。对Pax9周围一个扩展基因组区间的仔细检查显示，在人类、小鼠和河豚基因组中存在强烈的同线性保守。我们提出，多基因区域中顺式调控序列的这种交叉组织是维持进化保守同线性的一种可能机制。
